Investigation of Transdermal Drug Delivery and In Vivo Pharmacokinetics of Choline Ketoprofen Ionic Liquid.

To solve the bioavailability of nonsteroidal anti-inflammatory drugs and reduce their clinical risks, this study combined density functional theory (DFT) calculations with experiments and investigated the mechanism of in vitro transdermal absorption of choline ketoprofen gel and the pharmacokinetics of choline ketoprofen in rats. High-performance liquid chromatography (HPLC) was used to analyze the in vitro transdermal effect of ketoprofen in rats and the concentration of ketoprofen in the plasma of rats, which were administered choline ketoprofen by gavage. After the transdermal treatment, the rat skin was subjected to Hematoxylin and Eosin (H&E) staining and observe changes in skin structure. The results indicate that choline ketoprofen gel is superior to ketoprofen gel in terms of transdermal ability. Its transdermal rate is 1.4-2.2 times that of ketoprofen gel. The results show that the interaction force between choline ketoprofen and phospholipids is approximately 2.5 times that between ketoprofen and phospholipids, causing edema in epidermal cells and the dermis, which enlarges the intercellular space and then enhances the transdermal absorption capacity of ketoprofen. Compared with the ketoprofen suspension, the peak concentration of ketoprofen increased from 7.708 to 39.495 mg·L-1 (p < 0.05) for ketoprofen choline, and the relative bioavailability was 479.86%. It can be seen that the drug ionic liquid pathway can improve the absorption of drugs by the body and can better exhibit the dual functions of ionic liquids (penetration enhancers, surfactants, etc.) and drugs. These preliminary research results can lay the foundation for in-depth research on ketoprofen ionic liquid gels.